Fluorescence in situ hybridization (FISH) on enriched CD138 plasma cells is the standard method for identification of clinically relevant genetic abnormalities in multiple myeloma. However, FISH is a targeted analysis that can be challenging due to the genetic complexity of myeloma. The aim of this study was to evaluate the potential of optical genome mapping (OGM) to detect clinically significant cytogenetic abnormalities in myeloma and to provide larger pangenomic information. OGM and FISH analyses were performed on CD138-purified cells of 20 myeloma patients. OGM successfully detected structural variants (SVs) (IGHandMYCrearrangements), copy number variants (CNVs) (17p/TP53deletion, 1p deletion and 1q gain/amplification) and aneuploidy (gains of odd-numbered chromosomes, monosomy 13) classically expected with myeloma and led to a 30% increase in prognosis yield at our institution when compared to FISH. Despite challenges in the interpretation of OGM calls for CNV and aneuploidy losses in non-diploid genomes, OGM has the potential to replace FISH as the standard of care analysis in clinical settings and to efficiently change how we identify prognostic and predictive markers for therapies in the future. To our knowledge, this is the first study highlighting the feasibility and clinical utility of OGM in myeloma.
在富集CD138浆细胞上进行荧光原位杂交（FISH）是识别多发性骨髓瘤中临床相关遗传异常的标准方法。然而，由于骨髓瘤的遗传复杂性，FISH作为一种靶向分析可能具有挑战性。本研究旨在评估光学基因组图谱（OGM）检测骨髓瘤中具有临床意义的细胞遗传学异常的潜力，并提供更广泛的泛基因组信息。我们对20名骨髓瘤患者的CD138纯化细胞进行了OGM和FISH分析。OGM成功检测到骨髓瘤中典型预期的结构变异（SV）（IGH和MYC重排）、拷贝数变异（CNV）（17p/TP53缺失、1p缺失和1q增益/扩增）以及非整倍体（奇数号染色体增益、13号染色体单体），与FISH相比，在我们机构中使预后检出率提高了30%。尽管在非二倍体基因组中，OGM对CNV和非整倍体缺失的判读存在挑战，但OGM有潜力取代FISH成为临床环境中的标准护理分析，并有效改变我们未来识别治疗预后和预测标志物的方式。据我们所知，这是首次强调OGM在骨髓瘤中可行性和临床实用性的研究。
Optical Genome Mapping Reveals the Complex Genetic Landscape of Myeloma
肿瘤(癌症)患者之家